OBJECTIVES: This study was aimed to establish the most effective premature ovarian failure (POF) mouse model using Cyclophosphamide (CTX), busulfan (Bu), and cisplatin considering treatment duration of anticancer drugs and natural recovery time. METHODS: POF was induced by intraperitoneally injecting CTX (120 mg/kg)/Bu (12 mg/kg) for 1 to 4 weeks or cisplatin (2 mg/kg) for 3 to 14 days to C57BL/6 female mice aged 6 to 8 weeks. Controls were injected with equal volume of saline for the same periods. Body weight was measured every week, and ovarian and uterine weights were measured after the last injection of anticancer drug. To assess ovarian function, POF-induced mice were superovulated with pregnant mare serum gonadotropin and human chorionic gonadotropin, and then mated with male. After 18 hours, zygotes were retrieved and cultured for 4 days. Finally, the mice were left untreated for a period of times after the final injection of anticancer drug, and the time for natural recovery of ovarian function was evaluated. RESULTS: After 2 weeks of CTX/Bu injection, ovarian and uterine weights, and ovarian function were decreased sharply. Cisplatin treatment for 10 days resulted in a significant decrease in ovarian and uterine weight, and ovarian function. When POF was induced for at least 2 weeks for CTX/Bu and for at least 10 days for cisplatin, ovarian function did not recover naturally for 2 weeks and 1 week, respectively. CONCLUSIONS: These results suggest that CTX/Bu should be treated for at least 2 weeks and cisplatin for at least 10 days to establish the most effective primary ovarian insufficiency mouse model.
Animals ; Body Weight ; Busulfan ; Chorionic Gonadotropin ; Cisplatin ; Cyclophosphamide ; Female ; Gonadotropins ; Humans ; Male ; Mice ; Primary Ovarian Insufficiency ; Weights and Measures ; Zygote

OBJECTIVES: The aim of this study is to investigate the association between serum uric acid level and metabolic syndrome according to menopausal status in Korean women. METHODS: A total of 2,241 women who visited to the health promotion center at Pusan National University Hospital from 2010 to 2014 were included in this cross-sectional study. Self-report questionnaires and interviews with healthcare providers were used to assess disease history, medication history, menstrual history and body size measuring. Anthropometric measurements and laboratory results were compared as presence of metabolic syndrome and menopausal status by student-t test. Logistic regression analysis was performed between presence of metabolic syndrome and presumable predictive factors, such as age, menopause and serum uric acid. RESULTS: The prevalence rate of metabolic syndrome were 7.45% (63/846) in pre-menopausal group and 23.87% (333/1395) in menopausal group. Serum uric acid level was higher in menopausal women than premenopausal women (4.6 +/- 1.1 vs. 4.3 +/- 0.9. P = 0.000). And, its concentration was also higher in metabolic syndrome than normal women regarding of menopausal statue (premenopause 4.7 +/- 1.1 vs. 4.2 +/- 0.8, P = 0.001, menopause 4.9 +/- 1.3 vs. 4.5 +/- 1.0, P = 0.000). Multiple logistic regression analysis showed serum uric acid and age have relationship with metabolic syndrome (OR: 1.453, 95% confidence interval [CI]: 1.074-1.111, P = 0.000; OR: 1.092, 95% CI: 1.305-1.619, P = 0.000). CONCLUSION: We could find out some potential of uric acid as predictive factor for metabolic syndrome in premenopausal and menopausal group. Further investigation is required to clarify the relationship between serum uric acid, menopause and metabolic syndrome.
Body Size ; Busan ; Cross-Sectional Studies ; Female ; Health Personnel ; Health Promotion ; Humans ; Incidence* ; Logistic Models ; Menopause ; Metabolic Syndrome X ; Prevalence ; Surveys and Questionnaires ; Uric Acid*

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BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) has potential as a noninvasive neuromodulation treatment method for various neuropsychiatric disorders, and repeated sessions of rTMS are more likely to enhance the therapeutic efficacy. This study investigated neurophysiologic and spatiodynamic changes induced by repeated 1-Hz rTMS of the temporal cortex using transcranial magnetic stimulation (TMS) indices and fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: Twenty-seven healthy subjects underwent daily 1-Hz active or sham rTMS of the right temporal cortex for 5 consecutive days. TMS indices of motor cortical excitability were measured in both hemispheres daily before and after each rTMS session, and 2 weeks after the last stimulation. FDG-PET was performed at baseline and after the 5 days of rTMS sessions. RESULTS: All subjects tolerated all of the sessions well, with only three of them (11.1%) reporting mild transient side effects (i.e., headache, tinnitus, or local irritation). One-Hz rTMS decreased motor evoked potential amplitudes and delayed cortical silent periods in the stimulated hemisphere. Statistical parametric mapping of FDG-PET data revealed a focal reduction of glucose metabolism in the stimulated temporal area and an increase in the bilateral precentral, ipsilateral superior and middle frontal, prefrontal and cingulate gyri. CONCLUSIONS: Repeated rTMS sessions for 5 consecutive days were tolerated in all subjects, with only occasional minor side effects. Focal 1-Hz rTMS of the temporal cortex induces cortico-cortical modulation with widespread functional changes in brain neural networks via long-range neural connections.
Brain ; Evoked Potentials, Motor ; Glucose ; Headache ; Positron-Emission Tomography ; Salicylamides ; Tinnitus ; Transcranial Magnetic Stimulation

BACKGROUND: Triple negative breast cancer (TNBC) is defined as a lack of the expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 in breast cancer. Many TNBCs show a profound infiltration of tumor infiltrating lymphocytes (TILs). It is still uncertain whether these TILs are protumoral or antitumoral. Regulatory T cells (Tregs) play a role in inducing immune tolerance to antigens, and they may be selectively recruited by cancer cells. This study was conducted to evaluate the significance of TILs with an emphasis on forkhead box p3 (Foxp3), which is a marker for CD25+CD4+ Treg in TNBC. METHODS: We investigated the Foxp3, CD8 and CD4 expressions in 100 cases of TNBC by immunohistochemistry and using a tissue microarray. The Foxp3 expression was divided as the high and low infiltration groups (cut-off value=20). RESULTS: The high infiltration group was correlated with higher histologic and nuclear grades. However, Foxp3+ Tregs were decreased in the T3 and T4 TNBCs as compared to that of the T1 and T2 TNBCs. No significant differences were found for the nodal status, lymphovascular invasion, stage, recurrence and overall survival. CONCLUSIONS: High Foxp3+ Treg infiltration in TNBC is correlated with the nuclear and histologic grades, but there was no relation to recurrence and overall survival.
Breast ; Breast Neoplasms ; Estrogens ; Forkhead Transcription Factors ; Humans ; Immune Tolerance ; Immunohistochemistry ; Lymphocytes ; Lymphocytes, Tumor-Infiltrating ; Receptor, Epidermal Growth Factor ; Receptor, erbB-2 ; Receptors, Progesterone ; Recurrence ; T-Lymphocytes, Regulatory

BACKGROUND: The ABO antibody titration is important, especially in case of ABO-incompatible hemolytic disease of newborn, ABO-incompatible bone marrow or solid organ transplantation. However, no standard method for ABO antibody titration has yet been established. We surveyed four university hospitals about the methods of ABO antibody titration and performed inter-laboratory proficiency tests. METHODS: Detailed methods of ABO antibody titration were surveyed at four university hospitals. ABO antibody titer was measured by their customary methods using serum samples from six healthy volunteers with blood groups A (n=2), B (n=2) and O (n=2). RESULTS: Procedures of ABO antibody titration, reportable ranges, sample diluent, source of reagent RBCs and interpretation of end-point were different among four university hospitals. Inter-institutional maximum differences of IgM and IgG ABO antibody titer were 16-fold and 32-fold, respectively. CONCLUSION: Standardization of ABO antibody titration method is needed to reduce inter-laboratory variability, and a periodical external quality control survey is necessary to improve the accuracy of the titration.
Blood Group Antigens ; Bone Marrow ; Erythroblastosis, Fetal ; Hospitals, University ; Immunoglobulin G ; Immunoglobulin M ; Infant, Newborn ; Korea ; Organ Transplantation ; Quality Control ; Transplants

BACKGROUND: This study was done to obtain comprehensive data on changes in the structural components of the enteric nervous system in pediatric patients with intestinal pseudo-obstruction (IPO). We evaluated routinely processed, in formalin-fixed tissues by quantitative morphometric analysis. In addition, we used formalin-fixed tissue to explore the possibility of using previously proposed diagnostic criteria to evaluate frozen serial sections for intestinal neuronal dysplasia (IND) type B and hypoganglionosis. METHODS: We analyzed data for 19 IPO cases. Morphometric analysis for quantification of ganglia and ganglion cells (GCs) was done for the myentric and the submucous plexus. In addition, we determined the presence of immature GCs and the distribution of nerve fibers and interstitial cells of Cajal (ICC). RESULTS: Nine patients showed combined hypoganglionosis, IND, and decreased ICC; others showed various combinations of these. Several morphometric factors were significantly different between patient groups as well as being different than the control group. CONCLUSIONS: Our pediatric IPO cases showed extensive overlapping of pathological findings. And the findings suggest the utility of using previously proposed morphometrically measured factors in multiple frozen sections as diagnostic criteria for IND type B and hypoganglionosis in formalin-fixed tissue.
Enteric Nervous System ; Frozen Sections ; Ganglia ; Ganglion Cysts ; Humans ; Interstitial Cells of Cajal ; Intestinal Pseudo-Obstruction ; Nerve Fibers ; Neurons ; Submucous Plexus

BACKGROUND: Regulatory T cells (Tregs) may contribute to the immunological hyporesponsiveness against hepatitis B virus (HBV), and this can result in chronic infection. Tregs suppress the T cell responses directed against HBV and they protect hepatocytes by down-regulating the immune responses that cause liver damage, but the role of Tregs has not been well characterized. METHODS: Fifty four patients were selected and classified into three groups (12 were in the immune-tolerance phase, 35 were in the immune-clearance phase and 7 were in the asymptomatic virus carrier phase). We examined the frequency of CD3+, CD4+ & CD8+ T cells and forkhead box P3 (FoxP3)+ Tregs in the needle-biopsied liver tissue by performing immunohistochemistry. RESULTS: The FoxP3+ Tregs were mainly located at the portal tracts. In the immune-clearance phase, the frequency of FoxP3+ Tregs was significantly increased compared to that of the immune-tolerance group and the asymptomatic carrier group. Increased FoxP3+ T cells were observed in the patients with a higher histologic inflammatory index. No correlation was observed among the numbers of FoxP3+ Tregs, the serum alanine aminotransferase level, detection of HBeAg and the HBV-DNA viral load. CONCLUSIONS: FoxP3+ Tregs may play important roles in suppressing the immune response to HBV and the complete elimination of HBV.
Alanine Transaminase ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Hepatocytes ; Humans ; Liver ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Viruses

BACKGROUND: We report here the results of surveys for external quality assessment of blood bank tests performed in 2009. METHODS: Survey specimens were sent three times to 488, 491 and 490 participant institutes, and the response rates for the 1st, 2nd and 3rd trial were 97.7%, 98.0%, and 98.0%, respectively. Test items for the surveys were ABO grouping, Rh (D) typing, crossmatching, direct antiglobulin test, antibody screening and antibody identification test. RESULTS: The average accuracy rates of ABO grouping and Rh typing were 99.6-100% and 98.5-100%, respectively. In crossmatching test, the accuracy rates were 99.3-99.8% for the compatible samples, 92.7-100% for the incompatible samples, and 92.6-93.1% for the samples which could be detected as incompatible only by antiglobulin method. The accuracy rates of direct antiglobulin test were 98.5-100% for negative samples and 98.1-98.8% for positive samples. The correctresults were reported by 98.0-100% of the surveyed institutions for antibody screening test and 82.9-100% for antibody identification test. Nineteen institutions gave repeatedly incorrect answers for crossmatching test. Eight institutions out of them gave incorrect answers for all the test specimens sent out 3 times last year. CONCLUSIONS: The overall results of this survey were good, however, it is required that the institutions where the incorrect results were reported should perform corrective actions for quality improvement.
Academies and Institutes ; Blood Banks ; Coombs Test ; Korea ; Mass Screening ; Quality Improvement

BACKGROUND: This study was done to see if there were correlations between anatomic and molecular parameters such as microvessel density (MVD), lymphatic vessel density (LVD), and vascular endothelial growth factor receptor (VEGFR)-3 expression and various clinical parameters for papillary thyroid carcinomas of size > 1.0 cm (PTCs) and size < or = 1.0 cm (papillary thyroid microcarcinomas, PTMCs). PTMCs were divided into two subgroups (0-5 mm and 6-10 mm). METHODS: We analyzed 197 thyroid carcinomas including 113 PTCs and 84 PTMCs. Tissue samples form 30 patients from each group matched for clinical characteristics were selected for immunostaining. RESULTS: Although PTCs and PTMCs showed significant differences in clinical characteristics, they did not show significant difference in MVD, LVD, or VEGFR-3 expression. There was a significantly higher LVD in the PTMC subgroup with the larger tumors but no difference in clinical characteristics. LVD was higher in patients > 45 years old (more apparent in the PTC group) and LVD had suggestive correlations with multicentricity and extrathyroidal extension depending on analytic conditions. CONCLUSIONS: Since LVD showed variable correlations with clinical variables for papillary carcinoma of the thyroid depending on analytic conditions, the individually planned treatments based on overall clinicopathological factors are advised.
Carcinoma ; Carcinoma, Papillary ; Factor IX ; Glycosaminoglycans ; Humans ; Lymphangiogenesis ; Lymphatic Vessels ; Microvessels ; Neovascularization, Pathologic ; Receptors, Vascular Endothelial Growth Factor ; Thyroid Gland ; Thyroid Neoplasms ; Vascular Endothelial Growth Factor Receptor-3